Adrenal imaging with technetium-99m-labelled low density lipoproteins

Isaacsohn, Jonathan L.; Lees, Ann M.; Lees, Robert S.; Strausś, H. William; Barlai-Kovach, M; Moore, Thomas J.

doi:10.1016/0026-0495(86)90156-3

Cited by 23 publications

(10 citation statements)

References 8 publications

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“…Expression of LDL receptors in the liver can be decreased by a diet enriched in cholesterol and triglycerides rich in saturated fatty acids (Angelin et al 1983: Dietschy et al 1993: Packard et al 1983). The expression of LDL receptors in the spleen and adrenals can be significantly reduced by the administration of bile salts and corticosteroids respectively (Hynds et al, 1984: Isaacsohn et al 1986). …”

Section: Discussionmentioning

confidence: 99%

Low-density lipoprotein receptor-mediated delivery of a lipophilic daunorubicin derivative to B16 tumours in mice using apolipoprotein E-enriched liposomes

Versluis¹,

Rensen²,

Rump³

et al. 1998

Br J Cancer

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Summary Many tumours express relatively high levels of low-density lipoprotein (LDL) receptors on their membranes. The LDL receptor is, therefore, an attractive target for the selective delivery of antineoplastic drugs to tumour cells. We reported previously on the synthesis of small apolipoprotein E (apoE)-containing liposomes that behave in vivo in a very similar way to native LDL. In this study, we (LAD). Tissue distribution studies showed that LAD-loaded apoE liposomes were taken up and processed by the major LDL receptor-expressing organs (i.e. adrenals, liver and spleen). Of all other tissues, the tumour showed the highest uptake. The distribution pattems of LAD-loaded apoE liposomes and native LDL in the tumour-bearing mice were very similar, which supports the role of the LDL receptor in the disposition of the prodrug-loaded particles. The disposition of LAD followed the pattem of the liposomal carrier. We conclude that apoE liposomes enable LDL receptor-mediated specific delivery of antineoplastic (pro)

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Section: Discussionmentioning

confidence: 99%

Low-density lipoprotein receptor-mediated delivery of a lipophilic daunorubicin derivative to B16 tumours in mice using apolipoprotein E-enriched liposomes

Versluis¹,

Rensen²,

Rump³

et al. 1998

Br J Cancer

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“…28 After 1 hour, the animal was sacrificed by a lethal injection of pentobarbital. After sacrifice, the aorta was fixed in situ with formalin 18 and was then removed en bloc. The adventitia was removed completely and the remaining aorta was washed in formalin and divided into abdominal (ballooned) and thoracic (unballooned) regions.…”

Section: Aortic and Adrenal Specimensmentioning

confidence: 99%

“…Recently, we established that " T c -L D L can be employed for the external imaging of LDL accumulation by tissues, including the injured healing arterial wall and the adrenal cortex. 17 ' 18 Modification of native LDL by derivatization of the guanidino groups of arginyl residues with 1,2-cyclohexanedione or the epsilon-amino groups of lysyl residues by reductive methylation (MeLDL) abolishes the binding of the lipoprotein to LDL receptors, and causes the cellular uptake of these derivatized molecules to be mediated by apparently nonspecific mechanisms.…”

mentioning

confidence: 99%

Accumulation of native and methylated low density lipoproteins by healing rabbit arterial wall.

Fischman¹,

Lees²,

Lees

et al. 1987

Arteriosclerosis

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“…Uptake of LDL by tumour cells was found to be unaffected by the treatment (Hynds et al, 1984). The uptake of LDL by the adrenals was shown to be greatly reduced in rats and rabbits by the administration of corticosteroids like hydrocortisone or dexamethasone (Hynds et al, 1984;Isaacsohn et al, 1986). Thus, it is possible specifically to down-regulate LDL receptors on non-malignant cells, so that cytotoxic compounds can be selectively delivered to tumour cells by an LDL carrier.…”

Section: Discussionmentioning

confidence: 99%

Receptor-mediated uptake of low-density lipoprotein by B16 melanoma cells in vitro and in vivo in mice

Versluis¹,

Geel²,

Oppelaar³

et al. 1996

Br J Cancer

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Summary Selective delivery of cytotoxic anti-neoplastic drugs can diminish the severe side-effects associated with these drugs. Many malignant tumours express high levels of low-density lipoprotein (LDL) receptors on their membranes. Therefore, LDL may be used as a carrier to obtain selective delivery of anti-neoplastic drugs to tumours. The present study was performed to investigate the feasibility of the murine B16 tumour/mouse model for the evaluation of LDL-mediated tumour therapy. LDL binds with high affinity to LDL receptors on cultured B16 cells (Kd, 5.9+2.3 Yg ml -; Bmax, 206+23 ng LDL mg-1 cell protein). After binding and internalisation, LDL was very efficiently degraded: 724+ 19 ng LDL mg -cell protein h-'. Chloroquine and ammonium chloride completely inhibited the degradation of LDL by the B16 cells, indicating involvement of lysosomes. LDL receptors were down-regulated by 70% after preincubation of B16 cells with 300 jg ml-l LDL, indicating that their expression is regulated by intracellular cholesterol. To evaluate the uptake of LDL by the B16 tumour in vivo, tissue distribution studies were performed in C57/Bl mice inoculated with B16 tumours. For these experiments, LDL was radiolabelled with tyramine cellobiose, a non-degradable label, which is retained in cells after uptake. At 24 h after injection of LDL, the liver, adrenals and the spleen were found to be the major organs involved in LDL uptake, with tissue-serum (T/S) ratios of 0.82+0.08, 1.17 + 0.20 and 0.69 + 0.08 respectively. Of all the other tissues, the tumour showed the highest uptake of LDL (T/S ratio of 0.40+0.07). A large part of the LDL uptake was receptor mediated, as the uptake of methylated LDL was much lower. Although the LDL uptake by the liver, spleen and adrenals is higher than that by the tumour, the LDL receptor-mediated uptake by these organs may be selectively down-regulated by methods that do not affect the expression of LDL receptors on tumour cells. It is concluded that the B16 tumour-bearing mouse constitutes a good model to evaluate the effectiveness of LDL-mediated delivery of cytotoxic (pro)drugs to tumours in vivo.

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Adrenal imaging with technetium-99m-labelled low density lipoproteins

Cited by 23 publications

References 8 publications

Low-density lipoprotein receptor-mediated delivery of a lipophilic daunorubicin derivative to B16 tumours in mice using apolipoprotein E-enriched liposomes

Low-density lipoprotein receptor-mediated delivery of a lipophilic daunorubicin derivative to B16 tumours in mice using apolipoprotein E-enriched liposomes

Accumulation of native and methylated low density lipoproteins by healing rabbit arterial wall.

Receptor-mediated uptake of low-density lipoprotein by B16 melanoma cells in vitro and in vivo in mice

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